The now chronic nature of HIV has been a major advancement in AIDS care, but as with any chronic condition brings with it the recognition of other sequelae, including the HIV-associated neurocognitive disorder (HAND). In addition, as a natural consequence of the chronicity of infection and reduced new infection, the face of HIV infection is changing to an older population; soon over half of infected individuals will be 50 years of age or greater. As detailed in our Research Plan, we will now take the lessons others and we have learned about HIV and the brain and apply it to the changing epidemic - the graying of HIV, the nature of the effects on the brain of the chronic infection, means to treat HIV in the brain, and potential interaction with conditions linked to aging and other neurodegenerative disorders. We will set about this through the Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center as described in this proposal. We will accomplish four Action Items novel Biomarkers, the Role of Macrophages CNS Penetrating Antiviral Therapeutics, and the Effects on Chronic CNS Infection on Neurons, and support our investigators' research efforts through our Cores (Administrative, Biophysical Assessment Cells/Tissues/Animals, Developmental, International, Phenomics, Systems Biology, and Therapeutics). Our goals driven by our framework: researching of the chronicity of HIV infection in the CNS with a systems biology approach.